Neuronal activity in the vestibular nuclei after trigeminal stimulation.
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Response to constant angular accelerations of neurons in the monkey superior vestibular nucleus.
The response to constant angular acceleration of type I neurons in the superior vestibular nucleus was studied in pentobarbital-anesthetized, cerebellectomized squirrel monkeys. Some so-called intact animals had six active semicircular canals. In other animals, the three canals on one side were rendered non-responsive by plugging, and data were obtained from the plugged and unplugged sides. There is no significant difference between the mean resting activities of units from the plugged and unplugged sides and from intact animals. Two observations appear to reflect a synergy of inputs from parallel canals. First, units on the unplugged side have roughly linear excitatory input-output relationships. Some plugged-side units exhibit an excitatory saturation. The nonlinear excitatory input-output relation of units from intact animals may result from addition of ipsilateral linear and contralateral nonlinear inputs. Second, the mean sensitivity to angular acceleration of units on the plugged and unplugged sides is significantly smaller than that of units from intact animals. Units responsive to stimulation in either of two canal planes showed response summation with simultaneous activation of the two inputs. Type III and type IV responses can result from such summation.
Acceleration↗
Unbiased quantification of the microdissected human Scarpa's ganglion neurons.
OBJECTIVE: The objective of the present study was to obtain unbiased estimates of the total number of Scarpa's vestibular ganglion neurons in individuals with normal vestibular function. STUDY DESIGN: Application of unbiased stereology using microdissected human temporal bone specimens. METHODS: Postmortem temporal bones were obtained from five young subjects with no history of audiovestibular disease (age range 42-49 years). The vestibular nerve containing the Scarpa's ganglion was microdissected, embedded in paraffin, and cut into 40 microm serial sections. Unbiased estimates of the total number of neurons were obtained using the optical fractionator technique of stereology. RESULTS: An average of 23,599 (coefficient of variation [CV] = 0.11) vestibular ganglion neurons was obtained. There was no significant difference between the results obtained from the microdissected specimens and results that had been obtained from an age-matched group derived from a previously published report from our laboratory using archival human temporal bone specimens. CONCLUSIONS: This study represents the first report to demonstrate the combination of the microdissection technique and the unbiased stereologic technique in the human temporal bone. This study demonstrates the reliability of the microdissection technique as an alternative method of human temporal bone processing for unbiased stereology. The utility of the microdissection technique is that specimens can be used for quantification, immunohistochemistry, and other powerful applications.
Adult↗
Effects of stimulation of the vestibular nuclei on posterior hypothalamic neuron activity in guinea pigs.
To clarify the differences among the four main vestibular nuclei in the vestibulo-autonomic reflex, we examined the effects of electrical stimulation of superior, lateral, medial and descending vestibular nuclei (SVN, LVN, MVN and DVN) on posterior hypothalamic area (PHA) neurons in the guinea pig. Ipsi- and contralateral SVN stimulation produced excitation in 30% and 25% of the PHA neurons tested, respectively. Twenty percent of the PHA neurons showed an excitatory response to ipsilateral LVN stimulation while 60% of the neurons tested responded to contralateral LVN stimulation, including excitation of 36% and inhibition of 24%. MVN and DVN stimulation produced little change in PHA neuron activity. These findings suggest that vestibular information processed in the SVN and the LVN is conveyed to the hypothalamus and may then contribute to activation of the vestibulo-autonomic reflex.
Animals↗
A bilateral model integrating vergence and the vestibulo-ocular reflex.
The majority of previous modelling studies of vergence and the vestibulo-ocular reflex (VOR) have postulated arbitrary structures mainly on the basis of input-output behavioural relationships. Such models were developed following traditional schemes of oculomotor organization, based upon the notion of independence between different oculomotor subsystems. This impedes the simulation of complex binocular interactions and associated central activities. In contrast to preceding studies, the mathematical model for binocular control presented here was developed fully on physiological and anatomical grounds which reflect the organization and functional properties of known vergence and VOR premotor centres. Computer simulations show the model properly simulates the main observed characteristics in the discharge of several premotor and motor nuclei during slow vergence and the VOR in the dark. In particular, the model reproduces the activity profiles of abducens internuclear neurons, secondary vestibular cells, tonic prepositus hypoglossi neurons and ocular motoneurons during vergence and the VOR. It also simulates the activity of mesencephalic neurons whose discharge is modulated by vergence parameters alone. It is shown that given recent neurophysiological and behavioural findings, ocular reflexes cannot be properly modelled as separate independent subsystems whereas a single, unified modelling approach can produce results consistent with observed data. This study also shows how changes in the functional activity of shared pathways in a single two-sided structure produce vergence and conjugate integrators whose function relies on coupled loops across the brainstem: separate, dedicated operators are not necessary to replicate data. This provides evidence that challenges previous studies supporting the existence of separate vergence and conjugate integrators to transform velocity to position signals in the brainstem. A major implication of this study is that it questions the validity of testing conjugate and vergence systems independently, neglecting potential interactions.
Computer Simulation↗
Neuronal response sensitivity to bidirectional off-vertical axis rotations: a dimension of imbalance in the bilateral vestibular nuclei of cats after unilateral labyrinthectomy.
In decerebrate cats after acute hemilabyrinthectomy, the response sensitivity of extracellularly recorded vestibular nuclear neurons on the lesioned and labyrinth-intact sides were examined quantitatively during constant velocity off-vertical axis rotations with an aim to elucidate the functional contribution of otolithic inputs to the ipsilateral and contralateral vestibular nuclei. The bidirectional response sensitivity, delta, was determined as the ratio of the gain during clockwise to that during counterclockwise rotations. A continuum of response sensitivity was identified: one-dimensional neurons showed symmetrically bidirectional response patterns, while two-dimensional neurons showed asymmetrically bidirectional patterns that in some cases approached unidirectional patterns with change in velocity. The proportion of two-dimensional neurons was significantly increased after acute hemilabyrinthectomy. Two-dimensional neurons that responded only to one direction of rotation in at least one of the velocities tested were described as unidirectional neurons. This unidirectional response pattern was observed in one-third of the entire neuronal population studied, but not in cats with both labyrinths intact, thus suggesting that such prominent broadly tuned responses are normally masked by converging otolithic inputs from the contralateral side. These neurons were found in higher proportion on the lesioned side than on the labyrinth-intact side. Among the 70% of unidirectional neurons that exhibited bidirectional response at some velocities and unidirectional response at others, prominent shifts in delta values (i.e. between 0/infinity and finite values) with velocity can be computed for each neuron. The shifts in delta values correlated with large shifts in the response dynamics and spatial orientation as the response pattern changed with velocity. The response orientations of the unidirectional neurons pointed in all directions on the horizontal plane. When all the two-dimensional neurons (i.e. both the unidirectionally and bidirectionally responsive ones) were pooled, imbalances in the distribution of the response orientations and in response gain were found between the ipsilateral-side-down/head-down half-circle and the contralateral-side-down/head-up half-circle on the labyrinth-intact side, but not on the lesioned side. These results, derived from spatiotemporal processing of gravitational signals, reveal a novel dimension of imbalance between neuronal populations in the two vestibular nuclear complexes after acute lesion of one labyrinth. This feature would provide, on the one hand, deranged cues of spatial orientation and direction during slow head excursions and, on the other, a framework for the dynamic behavioral deficits associated with hemilabyrinthectomy.
Animals↗
A new vestibular thalamic area: electrophysiological study of the thalamic reticular nucleus and of the ventral lateral geniculate complex of the cat.
Single unit recordings were carried out in the reticularis thalamic nucleus (RT) and the ventral lateral geniculate body (LGv) of chronically prepared alert cats under sinusoidal vestibular stimulation in the horizontal plane. Optokinetic stimulation was also used. Of the 57 recorded neurons, 12 present vestibular modulation in the dark, analogous to Duensing's and Schaefer's (1958) type I response in the vestibular nuclei. Responses of 26 cells are similar to response of type II vestibular neurons and 14 units have a type III response; the 5 remaining cells were activated by vestibular stimulation in the vertical sagittal plane. The majority of these cells does not present detectable direct visual responses, but 50% can be driven by optokinetic stimulation. 74% of types I, II and III neurons show saccadic resonses to vestibular nystagmic saccades in the dark. About 60% present similar saccadic modulations during optokinetic nystagmus and 55% keep this response for spontaneous saccades in the dark or in front of a striped background. The saccadic responses are constant for a given neuron in all cases of stimulation with latencies ranging from 30 msec prior to the beginning of the saccade to 120 msec after its onset. The histological localization of these units falls on one hand into the caudal part of the RT nucleus (type III neurons) above the dorsal lateral geniculate nucleus and on the other hand within the internal subdivision of the LGv and its rostral limit (all other types). The significance of this new, saccadic and vestibular focus in the feline thalamus is discussed in relation with the two previously known vestibular thalamic relays in terms of interrelations between the vestibular and the visual systems.
Action Potentials↗
Phase relations of Purkinje cells in the rabbit flocculus during compensatory eye movements.
1. Purkinje cells in the rabbit flocculus that respond best to rotation about the vertical axis (VA) project to flocculus-receiving neurons (FRNs) in the medial vestibular nucleus. During sinusoidal rotation, the phase of FRNs leads that of medial vestibular nucleus neurons not receiving floccular inhibition (non-FRNs). If the FRN phase lead is produced by signals from the flocculus, then the Purkinje cells should functionally lead the FRNs. In the present study we recorded from VA Purkinje cells in the flocculi of awake, pigmented rabbits during compensatory eye movements to determine whether Purkinje cells have the appropriate firing rate phases to explain the phase-leading characteristics of the FRNs. 2. Awake rabbits were sinusoidally rotated about the VA in the light and the dark at 0.05-0.8 Hz with different amplitudes. The phase of the simple spike (SS) modulation in reference to eye and head position was calculated by determining the eye position sensitivity and the eye velocity sensitivity using multivariate linear regression and Fourier analysis. The phase of the SS modulation in reference to head position was compared with the phase of the FRN modulation, which was obtained in prior experiments with the same stimulus paradigms. 3. The SS activity of nearly all of the 88 recorded floccular VA Purkinje cells increased with contralateral head rotation. During rotation in the light, the SS modulation showed a phase lead in reference to contralateral head position that increased with increasing frequency (median 56.9 degrees at 0.05 Hz, 78.6 degrees at 0.8 Hz). The SS modulation led the FRN modulation significantly at all frequencies. The difference of medians was greatest (19.2 degrees) at 0.05 Hz and progressively decreased with increasing frequency (all Ps < 0.005, Wilcoxon rank-sum test). 4. During rotation in the dark, the SS modulation had a greater phase lead in reference to head position than in the light (median 110.3 degrees at 0.05 Hz, 86.6 degrees at 0.8 Hz). The phase of the SS modulation in the dark led that of the FRNs significantly at all frequencies (difference of medians varied from 24.2 degrees at 0.05 Hz to 9.1 degrees at 0.8 Hz; all Ps < 0.005). 5. The complex spike (CS) activity of all VA Purkinje cells increased with ipsilateral head rotation in the light. Fourier analysis of the cross-correlogram of the CS and SS activity showed that the phase lag of the CS modulation in reference to the SS modulation at 0.05 Hz in the light was not significantly different from that at 0.8 Hz (median 199.7 degrees at 0.05 Hz, 198.3 degrees at 0.8 Hz), even though the phases of the SS modulation at these two frequencies were significantly different (P < 0.001). These data indicate that the average temporal reciprocity between CS and SS modulation is fixed across the range of frequencies used in the present study. 6. The CS activity of most Purkinje cells did not modulate during rotation in the dark. Of 124 cases (each case consisting of the CS and SS data of a VA Purkinje cell obtained at 1 particular frequency) examined over the frequency range of 0.05-0.8 Hz, 17 cases (14%) showed CS modulation. In the majority (15 of 17) of these cases, the CS activity increased with contralateral head rotation; these modulations occurred predominantly at the higher stimulus velocities. 7. On the basis of the finding that FRNs of the medial vestibular nucleus lead non-FRNs, we predicted that floccular VA Purkinje cells would in turn lead FRNs. This prediction is confirmed in the present study. The data are therefore consistent with the hypothesis that the phase-leading characteristics of FRN modulation could come about by summation of VA Purkinje cell activity with that of cells whose phase would otherwise be identical to that of non-FRNs. The floccular SS output appears to increase the phase lead of the net preoculomotor signal, which is in part composed of the FRN and non-FRN signals.
Action Potentials↗
The fasciculus longitudinalis medialis in the lizard Varanus exanthematicus. 2. Vestibular and internuclear components.
In the present study the vestibular components of the fasciculus longitudinalis medialis (flm) were investigated in the lizard Varanus exanthematicus with various tracing techniques: anterograde transport of horseradish peroxidase to study vestibulo-oculomotor and vestibulospinal projections, the multiple retrograde fluorescent tracer technique for the cells of origin of such projections. Internuclear projections between the oculomotor and abducens nuclei could also be studied in this way. Rather extensive vestibulo-ocular projections passing via the flm were demonstrated. Mainly ipsilateral ascending projections arise in the dorsolateral vestibular nucleus, mainly contralateral ascending projections in the ventromedial vestibular nucleus and adjacent parts of the ventrolateral and descending vestibular nuclei. Furthermore, distinct bilateral ascending projections of the nucleus prepositus hypoglossi were demonstrated. Extensive vestibulospinal projections pass via the flm and form the medial vestibulospinal tract. This largely contralateral descending pathway arises predominantly in the ventromedial and descending vestibular nuclei. Terminal structures presumably arising in the ventromedial and descending vestibular nuclei were found on contralateral neurons, probably motoneurons innervating neck muscles. Vestibular neurons with both ascending (presumably to extra-ocular motoneurons) and descending projections to the spinal cord are present in all vestibular nuclei, although preferentially in the ventromedial vestibular nucleus and adjacent parts of the ventrolateral and descending vestibular nuclei. However, also in the dorsolateral vestibular nucleus a substantial number of double labeled neurons were found. These vestibular neurons with both vestibulomesencephalic and vestibulospinal projections are probably involved in combined movements of eyes and head. Evidence for reciprocal internuclear connections between the oculomotor and abducens nuclei was found. Neurons in the dorsal part of the oculomotor nucleus probably project to the ipsilateral abducens nucleus, while neurons in the abducens nucleus most likely project to the contralateral oculomotor nucleus. These reciprocal internuclear connections between the oculomotor and abducens nuclei probably play an important role in conjugate horizontal eye movements.
Animals↗
Expression of GATA-2 in the developing avian rhombencephalon.
Here we describe the expression pattern of GATA-2 in the developing chick hindbrain. We found that during the early period of neurogenesis this gene specifically labels a particular neuronal subtype, the contralateral vestibular-acoustic neurons of rhombomere 4, and that expression of this gene in these cells is transient. We also found that GATA-2 labels a broader territory of the ventral neural tube at later stages. As well as this hindbrain expression, we also describe expression of GATA-2 in the otic vesicle, oculomotor nucleus, third nerve and metanephros.
Animals↗
Central projections of primary vestibular fibers in the bullfrog: I. The vestibular nuclei.
The central projections of the vestibular end organs in the bullfrog Rana calesbeiana were analyzed by using horseradish peroxidase labeling of the primary vestibular afferents. Separate extracellular injections were made of the anterior branch, the posterior branch, the ampullary nerve of each of the three semicircular canals, and the branch to the saccule. The anterior and posterior branches of the bullfrog eighth nerve, each containing both vestibular and auditory fibers, merge and enter the brain stem as a single nerve root. The thin caliber fibers of the anterior branch enter the brain stem on the ventral-posterior aspect of the nerve and immediately divide dichotomously into ascending (rostral) and descending (caudal) branches. The thick caliber fibers of the anterior branch enter the brain stem on the ventral-anterior aspect of the eighth nerve and traverse medially into the alar plate before dividing into ascending and descending branches. The primary afferent fibers of the vestibular nerve innervate an ipsilateral area of the brain stem which extends caudally from the rhombencephalon at the level of the twelfth nerve nucleus and rostrally up to and including the cerebellar nucleus and the cerebellum. The following vestibular nuclei can be identified by the fact that they receive primary vestibular afferents: the ventral vestibular nucleus, medial vestibular nucleus, descending vestibular nucleus, superior vestibular nucleus, and cerebellar nucleus. The dorsal (acoustic) nucleus, which receives primary auditory input, also receives afferents from the saccule. In addition to these nuclei, the cerebellum and the reticular formation receive significant primary input from the various vestibular receptors. The primary vestibulo-cerebellar fibers terminate mainly among the granular cells of the lobus auricularis and of the corpus cerebelli on the ipsilateral side. Each of the three semicircular canals projects into the cerebellum, while no such projection was observed in the saccular nerve preparations. Fibers from each of the three semicircular canals project to all of the vestibular nuclei. Heavily labeled large neurons, presumably vestibular efferents, are seen in the ipsilateral reticular formation, adjacent to the seventh motor nucleus.
Animals↗
Time course of inner ear degeneration and deafness in mice lacking the Kir4.1 potassium channel subunit.
The Kir4.1 gene (KCNJ10) encodes an inwardly rectifying K(+) channel subunit abundantly expressed in the CNS. Its expression in the mammalian inner ear has been suggested but its function in vivo in the inner ear is unknown. Because diverse human hereditary deafness syndromes are associated with mutations in K(+) channels, we examined auditory function and inner ear structure in mice with a genetically inactivated Kir4.1 K(+) channel subunit. Startle response experiments suggest that Kir4.1-/- mice are profoundly deaf, whereas Kir4.1+/- mice react like wild-type mice to acoustic stimuli. In Kir4.1-/- mice, the Reissner membrane is collapsed, the tectorial membrane is swollen, and type I hair cells and spiral ganglion neurons as well as their central processes degenerate over the first postnatal weeks. In the vestibular ganglia, neuronal cell death with apoptotic features is also observed. Immunostaining reveals that Kir4.1 is strongly expressed in stria vascularis of wild-type but not Kir4.1-/- mice. Within the spiral ganglion, Kir4.1 labeling was detected on satellite cells surrounding spiral ganglion neurons and axons. We conclude that Kir4.1 is crucial for normal development of the cochlea and hearing, via two distinct aspects of extracellular K(+) homeostasis: (1). in stria vascularis, Kir4.1 helps to generate the cochlear endolymph; and (2). in spiral and vestibular ganglia, Kir4.1 in surrounding glial cells helps to support the spiral and vestibular ganglion neurons and their projecting axons.
Animals↗
Effects of eperisone applied by microiontophoresis on neurons in the medial and lateral vestibular nuclei.
Electrophysiological studies were performed to elucidate the mechanism underlying the antivertigo action of eperisone, an antispastic drug, using cats anesthetized with alpha-chloralose. Iontophoretic application of eperisone up to 100 nA produced a dose-dependent inhibition of spike generation upon vestibular nerve stimulation in monosynaptic and polysynaptic neurons of the medial vestibular nucleus (MVN). The inhibition of neurons in the MVN was more prominent than that in the lateral vestibular nucleus. In addition, iontophoretically applied eperisone in doses of 50-100 nA inhibited the orthodromic spike elicited by vestibular nerve stimulation in the MVN monosynaptic neurons projecting to the abducens nucleus (ascending neuron), without affecting that in the MVN neurons projecting to the spinal cord (descending neuron). An inhibition of antidromic spike elicited by abducens nucleus stimulation in the MVN monosynaptic ascending neurons was observed in some cases during application of eperisone. These results suggest that eperisone predominantly inhibits synaptic transmission of the MVN ascending neurons.
Animals↗
[Electrotonic coupling between the giant neurons of the lateral vestibular nucleus in the rat].
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Action Potentials↗
Target neurons of floccular middle zone inhibition in medial vestibular nucleus.
Unitary activities of 288 neurons were recorded extracellularly in the medial vestibular nucleus (MV) in anesthetized cats. In 19 neurons, located in the rostral part of the MV adjacent to the stria acustica, floccular middle zone stimulation resulted in cessation of spontaneous discharges. Systematic microstimulation in the brainstem during recording of 16 of 19 target neurons of floccular middle zone inhibition revealed that the target neurons projected to the ipsilateral abducens nucleus (ABN), and not to the contralateral ABN nor the oculomotor nucleus. The conjugate ipsilateral horizontal eye movement elicited by middle zone stimulation may be mediated by this pathway to motoneurons and internuclear neurons in the ipsilateral ABN. In additional experiments, the MV neurons responding antidromically to ipsilateral ABN stimulation and orthodromically to ipsilateral 8 nerve stimulation were recorded extracellularly. In only 7 of 36 recorded neurons, middle zone stimulation depressed the orthodromic and spontaneous activities. Many neurons were free of floccular inhibition. As to the route of floccular inhibitory control over the vestibulo-ocular reflex (VOR) during visual-vestibular stimulation, we propose that the interaction of target and VOR relay neurons takes place at the ipsilateral ABN and modulates the VOR, in addition to well known Ito's proposal that the interaction of the floccular output and the VOR takes place at secondary vestibular neurons and modulates the VOR.
Animals↗
Convergence and interaction of neck and macular vestibular inputs on reticulospinal neurons.
Extracellular recordings were obtained in decerebrate cats from neurons located in the inhibitory area of the medullary reticular formation, namely in the medial aspects of the nucleus reticularis gigantocellularis, magnocellularis and ventralis. Of 127 medullary reticular units examined, 77 were reticulospinal neurons antidromically identified following stimulation of the spinal cord at T12-L1; the remaining 50 neurons were not activated antidromically. Unit firing rate was analyzed under separate stimulation of macular vestibular, neck, or combined receptors by using sinusoidal rotations about the longitudinal axis at 0.026 Hz, 10 peak amplitude. Among the 127 reticular units, 84 (66.1%) responded with a periodic modulation of their firing rate to roll tilt of the animal and 93 (73.2%) responded to neck rotation. Convergence of macular and neck inputs was found in 71/127 (55.9%) reticular neurons; in these units, the gain as well as the sensitivity of the first harmonic of response corresponded on the average to 0.49 +/- 0.41, SD imp/s/deg and 5.10 +/- 4.27, SD %/deg for the neck responses and to 0.40 +/- 0.39, SD imp/s/deg and 3.90 +/- 3.80, SD %/deg for the macular responses, respectively. Most of the convergent reticular units were maximally excited by the direction of stimulus orientation, the first hormonic or responses showing an average phase lead of about +42.7 with respect to neck position and +24.9 with respect to animal position. Two populations of convergent neurons were observed. The first group of units (58/71, i.e. 81.7%) showed reciprocal ("out of phase") responses to the two inputs in that they were mainly excited during side-down neck rotation, but inhibited during side-down animal tilt. The remaining group of units (13/71, i.e. 18.3%) showed parallel ("in phase") responses to the two inputs and they were mainly excited by side-down neck rotation and animal tilt. The response characteristics of medullary reticular neurons to the combined neck and macular inputs, elicited during head rotation, closely corresponded to those predicted by a vectorial summation of the individual neck and macular responses. In particular, "out of phase" units displayed small amplitudes and large phase leads of the responses with respect to head position, when both types of receptors were costimulated. In contrast, "in phase" units displayed large amplitude and small phase leads during head rotation.(ABSTRACT TRUNCATED AT 400 WORDS)
Afferent Pathways↗
[Selective inhibition of neuronal activities in lateral vestibular nucleus in the rat under cerebral hypoxia].
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Animals↗
Molecular characterization of two novel splice variants of G alphai2 in the rat vestibular periphery.
GTP binding proteins play an important role in mediating signals transduced across the cell membrane by membrane-bound receptors. We previously described a partial sequence, termed Galphai2vest, obtained from rat vestibular tissue that was nearly identical to rat Galphai2. Using an experimental strategy to further characterize Galphai2vest (GenBank accession number AF189020) and identify other possible Galphai2-related transcripts expressed in the rat vestibular periphery, we employed a RecA-based gene enrichment protocol in place of conventional library screening techniques. We identified two novel Galphai2 splice variants, Galphai2(a) (GenBank accession number AY899210) and Galphai2(b) (GenBank accession number AY899211), that have most of exons 8 and 9 deleted, and exons 5 through 9 deleted, respectively. In situ hybridization studies were completed to determine the differential expression of Galphai2 between the vestibular primary afferent neurons and the vestibular end organs. Computer modeling and predicted 3D conformation of the wild type Galphai2 and the two splice variants were completed to evaluate the changes associated with the Gbetagamma and GTP binding sites. These two novel alternatively spliced isoforms of Galphai2 putatively encode truncated proteins that could serve unique roles in the physiology of the vestibular neuroepithelium. Galphai2vest was found to be a processed pseudogene.
Alternative Splicing↗